Abstract Developing synthetic bone scaffolds that simultaneously meet mechanical, structural and biological requirements for load‐bearing applications remains a major challenge in bone tissue engineering. Traditional fabrication routes often suffer from poor phase control, limited bioactivity or complex multi‐step processes. In this study, we present a scalable one‐shot synthesis strategy for fabricating nanohydroxyapatite (nHA) reinforced polyurethane scaffolds tailored for bone repair. A series of ester‐based polyester polyols were synthesized by reacting succinic acid with 1,4‐butanediol (BDO) and diethylene glycol (DEG) at varying ratios and molecular weights. Among them, PB 75 DES300 (75:25 BDO:DEG, ca 300 g mol −1 ) emerged as the optimal formulation, combining mechanical strength, thermal stability and processability. Incorporation of nHA during polyester synthesis promoted uniform nanoparticle dispersion and enhanced scaffold architecture. At 1.5 wt% nHA, the scaffold achieved a 31% increase in compressive modulus and marked improvement in microphase separation, while maintaining high porosity. SEM and swelling analyses confirmed improved pore regularity and water absorption, and human mesenchymal stem cell culture demonstrated significantly enhanced cell adhesion. These results highlight the dual role of nHA as both a mechanical reinforcer and a bioactive agent. The proposed one‐pot method enables precise control over scaffold structure and composition, offering a robust and clinically relevant platform for bone regeneration. © 2026 Society of Chemical Industry.
Azizollahi et al. (Wed,) studied this question.